Arrays of microneedles were proposed as a way of administering drugs through the skin in the 1970s, for example in expired U.S. Pat. No. 3,964,482. Microneedle or microstructure arrays can facilitate the passage of drugs through or into human skin and other biological membranes in circumstances where ordinary transdermal administration is inadequate. Microstructure arrays can also be used to sample fluids found in the vicinity of a biological membrane such as interstitial fluid, which is then tested for the presence of biomarkers.
In recent years it has become more feasible to manufacture microstructure arrays in a way that makes their widespread use financially feasible. U.S. Pat. No. 6,451,240 discloses some methods of manufacturing microneedle arrays. If the arrays are sufficiently inexpensive, for example, they may be marketed as disposable devices. A disposable device may be preferable to a reusable one in order to avoid the question of the integrity of the device being compromised by previous use and to avoid the potential need of resterilizing the device after each use and maintaining it in controlled storage.
Despite much initial work on fabricating microneedle arrays in silicon or metals, there are significant advantages to polymeric arrays. U.S. Pat. No. 6,451,240 discloses some methods of manufacturing polymeric microneedle arrays. Arrays made primarily of biodegradable polymers also have some advantages. U.S. Pat. No. 6,945,952 and U.S. Published Patent Applications Nos. 2002/0082543 and 2005/0197308 have some discussion of microneedle arrays made of biodegradable polymers. A detailed description of the fabrication of a microneedle array made of polyglycolic acid is found in Jung-Hwan Park et al., “Biodegradable polymer microneedles: Fabrication, mechanics, and transdermal drug delivery,” J. of Controlled Release, 104:51-66 (2005). These biodegradable microstructure arrays (MSA) may consist of a biodegradable tip portion containing a dried active pharmaceutical ingredient (API) and excipients in a biocompatible and water soluble polymer matrix. A backing portion, which connects and supports the tips, may consist of a biocompatible, non-water soluble polymer matrix. Once the MSA penetrates into the subject's skin, the tip portion rapidly dissolves and released the API very quickly, resulting in a fast Tmax.
A layered microstructure array has been described for hPTH delivery (U.S. Patent No. 2011/0276028) comprising a fast dissolving drug-in-tip distal layer and a backing layer formed of an insoluble biodegradable polymer. Administration of these microstructure arrays typically lead to fast dissolution of the distal layer and corresponding fast systemic absorption of the drug.
Many drugs require sustained delivery for a prolonged period of time including hours, days, weeks, etc. One approach for sustained delivery uses microprojection arrays with detachable microprojections such as in U.S. Pat. No. 8,366,677 and U.S. Application No. 61/745,513, (filed Dec. 21, 2012), which is incorporated herein by reference.
Therefore, there is a need for a microstructure array that provides for sustained or extended delivery of a therapeutic agent. Furthermore, there is a need to modulate or modify the drug release profile from the microstructure array in order to meet therapeutic requirements for therapeutic agents.
The microstructure arrays are preferably retained on or at the administration site for a period of time for a suitable or desired delivery of the therapeutic agent. One approach for maintaining the array at the delivery site uses a microneedle device that is applied to skin and adhered using a pressure sensitive adhesive surrounding the microneedle array, e.g. U.S. Pat. No. 8,267,889. This approach does not hold the microneedles closely to the skin except at the perimeter of the array where the adhesive contacts the skin and the edge of the array. U.S. Pat. No. 7,184,826 describes the use of microblades for piercing the skin to enhance delivery. To anchor the microblades, they may include a prong or barb extending from the microblades or include a partial adhesive coating. Microneedle arrays including a coating comprising a therapeutic agent coating have also been described, e.g. U.S. Pat. No. 8,057,842.
Thus, there is also a need in the art for microprojection arrays suitable for extended wear that provide better adhesion of the microprojection array and/or better contact of the microprojections and/or arrays.
The foregoing examples of the related art and limitations related therewith are intended to be illustrative and not exclusive. Other limitations of the related art will become apparent to those of skill in the art upon a reading of the specification and a study of the drawings.